CHOLESTEROL GALLSTONE FORMATION AND PREVENTION BY CHENODEOXYCHOLIC AND URSODEOXYCHOLIC ACIDS - NEW HAMSTER MODEL

  • 1 January 1979
    • journal article
    • research article
    • Vol. 77  (4) , 634-641
Abstract
Prior animal models of cholesterol gallstone formation were criticized for their dissimilarity to the conditions of humans with gallstones. A new hamster model of cholesterol choleithiasis that more closely approximates the human situation is presented. Sixty female Golden Syrian hamsters (average weight 86.2 .+-. 3.4 g) were allocated to 6 groups of 10 animals each. Groups were fed standard diet (containing 0.8 g cholesterol/g of food) or increased cholesterol diet (containing 2.4 mg cholesterol/g of food), with or without ethinyl estradiol, 15 .mu.g/kg per d [day]. Two groups receiving both increased cholesterol and ethinyl estradiol also received either chenodeoxycholic acid or ursodeoxycholic acid, 20 mg/kg per d. The animals were sacrified at 12 wk. Cholesterol gallstones (78.3 .+-. 5.0% cholesterol by weight) formed in 30% of the animals fed by ethinyl estradiol, 50% of those fed increased cholesterol and 90% of those fed the combination of both. Bile was saturated in all 3 groups, with the saturation index of the combination group (2.08 .+-. 0.17) being the highest. In both groups receiving bile acid therapy, no gallstones were found and the bile remained unsaturated. For the bile acid-fed groups, both hepatic HMG-CoAR [hydroxymethylglutaryl-CoA reductase] and hepatic cholesterol 7.alpha.-hydroxylase activities were reduced (P < 0.01) when compared to the group fed standard diet and to the group fed the combination. A new animal model of cholesterol gallstone formation was developed in which chenodeoxycholic acid and ursodeoxycholic acid therapy prevented gallstone formation through mechanisms similar to those reported in cholesterol gallstone patients.